Epinephrine Spray Formulation Rapid Onset Anaphylaxis

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Solution Overview

Problem

Current epinephrine formulations lack a quick-onset spray formulation for effective treatment of anaphylaxis, which is a life-threatening allergic reaction requiring immediate relief.

Innovation Solution

Development of epinephrine spray formulations containing 0.1% to 15% w/w epinephrine or its salts, with a solvent combination of water, ethanol, and propylene glycol, and a permeation enhancer like caprylic acid, designed to be propellant-free, with a pH range of 2 to 5.5, enhancing bioavailability and rapid onset of action.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If epinephrine is formulated as injection or auto-injector, then reliable treatment of anaphylaxis is achieved, but quick onset of action and ease of operation are compromised

Engineering Contradiction:
Improveonset of actionVSAvoidadministration convenience
Core Design Contradiction:
SpeedVSEase of operation

Solution Approach 1:

The patent changes the physical state parameter of epinephrine from liquid injection to aerosol spray formulation. This parameter change enables rapid delivery of epinephrine to the respiratory tract and systemic circulation through inhalation, achieving quick onset of action while maintaining ease of operation through simple spray administration

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses aerosol technology (pneumatic principle) to deliver epinephrine as a fine mist that can be inhaled deeply into the lungs. The propellant-based aerosol system enables rapid distribution of the drug throughout the respiratory tract, achieving both quick onset and easy administration

Inventive Principle:
Principle #29Pneumatics and hydraulics

2Speed

If epinephrine spray formulation is developed, then quick onset of action is achieved, but formulation stability and reliability are compromised

Engineering Contradiction:
Improveonset of actionVSAvoidformulation stability
Core Design Contradiction:
SpeedVSReliability

Solution Approach 1:

The patent uses a composite formulation system combining epinephrine with specific excipients including hydrophilic colloids (sodium carboxymethylcellulose, polyvinyl alcohol), surfactants (polysorbates), and buffers. This composite formulation maintains sprayability and rapid onset while ensuring formulation stability and reliability during storage

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent introduces intermediary substances (excipients such as sodium carboxymethylcellulose, polysorbate 80, and phosphate buffers) that mediate between the active ingredient epinephrine and the aerosol delivery system. These intermediaries stabilize the formulation, prevent degradation, and maintain spray characteristics without compromising the quick onset of action

Inventive Principle:
Principle #24Intermediary (Mediator)

3Ease of operation

If propellant is included in spray formulation, then spray delivery is achieved, but harmful factors and safety are compromised

Engineering Contradiction:
Improvespray deliveryVSAvoidsafety
Core Design Contradiction:
Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The patent changes the propellant parameters by using hydrofluoroalkane (HFA) propellants with optimized vapor pressure and boiling point characteristics. This parameter change enables effective spray delivery while reducing harmful effects compared to traditional chlorofluorocarbon propellants, improving safety and environmental compatibility

Inventive Principle:
Principle #35Parameter changes

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The formulations demonstrate improved bioavailability, rapid onset of action, and enhanced storage stability, effectively treating anaphylaxis through intranasal or sublingual administration, providing consistent and stable epinephrine delivery.

Implementation Method 1

the formulation further comprises a permeation enhancer comprising caprylic acid

Methodology Applied
Scientific EffectPermeation enhancement: Permeation

Implementation Method 2

Epinephrine binds to these adrenergic receptors leading to relief of many life-threatening symptoms

Methodology Applied
Scientific EffectReceptor binding: Chemical Bonding

Data Source

PatentUS10039710B2Epinephrine spray formulations
Publication Date: 2018.08.07 HIKMA PHARMACEUTICALS USA INC

AI summary

The present invention is directed to epinephrine spray formulations. The present invention is further directed to methods of treating anaphylaxis by administering epinephrine spray formulations to subjects in need of such treatments.